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Published: 2026-04-27

Keywords:QbD, Novel drug delivery system, Proniosomal Gel, Crisaborole, Coacervation Phase separation Method,Zero-order kinetics,.

ABSTRACT

The present research focused on the QbD-assisted formulation and development of a phytosomal gel containing Crisaborole and Barbaloin, aimed at improving their solubility, bioavailability, dermal permeation, and therapeutic efficiency. Extensive pre-formulation studies confirmed the physicochemical suitability of both drugs, including acceptable organoleptic properties, solubility profiles, pH, melting point, and functional group compatibility through FTIR analysis. The solubility limitations of both drugs, especially the poor aqueous solubility of Crisaborole, justified the need for a lipid-based nanocarrier such as phytosomes. UV spectral analysis and calibration curve development enabled accurate quantification during formulation and evaluation. Using Design of Experiments (DoE) with a Box–Behnken design, three critical formulation variables—soya lecithin, cholesterol, and sonication time were statistically optimized for two major responses: particle size and entrapment efficiency. The linear model was identified as the best fit for both responses, with sonication time showing the most significant influence. Among the 12 formulations, the optimized batch exhibited a nanoscale particle size (177.09 nm), high entrapment efficiency (91.80%), and desirability of 1.0, indicating excellent alignment between predicted and actual values. SEM analysis confirmed well-formed, spherical, and uniform phytosomal nanoparticles. The optimized phytosomes were successfully incorporated into a gel base, producing a formulation with ideal organoleptic properties, skin-friendly pH, appropriate viscosity, excellent spreadability, and no skin irritation, demonstrating suitability for topical use. The in-vitro release study showed a sustained release of 95.25% over 16 hours, following Zero-order kinetics (R² = 0.980), indicating controlled and consistent drug delivery. Overall, the study effectively demonstrated that QbD and DoE approaches significantly enhanced formulation precision, process understanding, and product quality.